Optic nerve oxygen tension in pigs and the effect of carbonic anhydrase inhibitors

PURPOSE. To evaluate how the oxygen tension of the optic nerve (ONPo2) is a ffected by the administration of the carbonic anhydrase inhibitors dorzolam ide and acetazolamide and by alterations in oxygen and carbon dioxide in th e breathing mixture. METHODS. Polarographic oxygen electrodes were placed in the vitreous humor immediately over the optic disc in 20 anesthetized pigs. Blood gasses and c ardiovascular physiology were monitored. ONPo2 was recorded continuously wi th breathing gasses of 21% O-2-79% N-2, 100% O-2, 20% O-2-80% N-2, and 5.19 % CO2-19.9% O-2-74.9% N-2. Acetazolamide (15-1000 mg) and dorzolamide (6-10 00 mg) were administered intravenously. RESULTS. The mean(+/- SD) ONPo2 was found to be 24.1 +/- 11.6 mm Hg when the pigs were breathing room air and 50.7 +/- 29.3 mm Hg when they were breathing 100% O-2 (n = 15; P < 0.001). In response to breathing 5.19% CO2, ONPo2 changed from 20.8 +/- 5.6 mm Hg ( with 20.0% O-2) to 28.9 +/- 3.6 mm Hg (n = 4; P < 0.001). Intravenous injec tions of 500 mg dorzolamide increased ONPo2 from 16.4 +/- 6.1 mm Hg to 26.9 +/- 12.2 mm Hg, or 52.5% +/- 21.2% (n = 5; P = 0.017). A dose-dependent ef fect on ONPo2 was seen with intravenous dorzolamide doses of 1000, 500, 250 , 125, 63, 27, 15, and 6 mg. Intravenous injections of 500 mg acetazolamide increased ONPo2 from 23.6 +/- 9.5 mm Hg to 30.9 +/- 10.0 mm Hg (n = 6; P < 0.001), and a dose-dependent effect was seen with closes of 1000, 500, 250 , 125, 31, and 15 mg. CONCLUSIONS. ONPo2 is significantly increased by the carbonic anhydrase inh ibition of dorzolamide and acetazolamide, and the effect is dose dependent. These data demonstrate for the first time a direct effect of carbonic anhy drase inhibitors on ONPo2.